Bone Morphogenetic Protein Glass Bottom Boat (BMP5/6/7/8) and its receptor Wishful Thinking (BMPRII) are required for injury-induced allodynia in Drosophila.

Abstract

BackgroundChronic pain affects millions of people worldwide; however, its cellular and molecular mechanisms have not been completely elucidated. It is thought that chronic pain is triggered by nociceptive sensitization, which produces elevated nocifensive responses. A model has been developed in Drosophila melanogaster to investigate the underlying mechanisms of chronic pain using ultraviolet-induced tissue injury to trigger thermal allodynia, a nociceptive hypersensitivity to a normally innocuous stimulus. Larvae were assayed for their behavioral latencies to produce a distinct avoidance response under different thermal conditions. Previously, Decapentaplegic, a member of the Bone Morphogenetic Protein (BMP) family and orthologous to mammalian BMP2/4, was shown to be necessary for the induction of allodynia. Here, we further investigate the BMP pathway to identify other essential molecules necessary to activate the nociceptive sensitization pathway.ResultsUsing the GAL4-UAS-RNAi system to induce a cell-specific knockdown of gene expression, we further explored BMP pathway components to identify other key players in the induction of nociceptive sensitization by comparing the responses of manipulated animals to those of controls. Here, we show that a second BMP, Glass Bottom Boat, and its receptor Wishful Thinking are both necessary for injury-induced thermal allodynia since the formation of sensitization was found to be severely attenuated when either of these components was suppressed. The effects on pain perception appear to be specific to the sensitization system, as the ability to respond to a normally noxious stimulus in the absence of injury was left intact, and no nociceptor morphological defects were observed.ConclusionThese results provide further support of the hypothesis that the BMP pathway plays a crucial role in the development of nociceptive sensitization. Because of its strong conservation between invertebrates and mammals, the BMP pathway may be worthy of future investigation for the development of targeted treatments to alleviate chronic pain.